Several related aspects of the metabolic control of transcription and catalysis will be investigated. The molecular genetics of the trpR gene-tryptophan repressor protein system will be elucidated by isolating a specialized transducing derivative of phage lambda where one or more phage genes has been substituted by the trpR gene of Escherichia coli. A family of deletions which remove all or part of the trpR gene will be characterized, and used to study the mechanisms which control the intracellular levels of trp repressor protein. We have previously established that trp operon DNA (6800 base pairs) contains several sets of sequences which can undergo mutational change to create a promoter, or site for the initiation of transcription. One such site has been intensively studied by exploiting the Trp phenotype; this led to the realization that several synonymous sequences, all having identical promoter activity, exist. Work in the coming year will be directed toward establishing the pertinent sequence of bases in DNA. The isolation of fluorine-substituted analogs of intermediates in the shikimate pathway will also be actively pursued during the coming year. The immediate goal is to obtain a sample of 2-fluorochorismic acid, then study the interaction of this compound with anthranilate synthase, in order to elucidate the catalytic mechanism of an important biological aromatization reaction. This enzyme is of considerable interest because it catalyzes the regulated step in tryptophan biosynthesis and because it is subject to a multiplicity of conformational changes. BIBLIOGRAPHIC REFERENCES: L.-M. Yang and R. L. Somerville. Purification and Properties of a New Amino-peptidase from Escherichia coli K-12. Biochimica et Biophysica Acta 445, 406-419 (1976). B. Hausler and R. L. Somerville. On the Degeneracy of Promoter Structure. Fed. Proc. 36 (1977).